Human factor IX protein domain architecture, where each protein domain is represented by a coloured box

The N-terminal EGF domain has been shown to at least in part be responsible for binding tissue factor.[5] Wilkinson et al. conclude that residues 88 to 109 of the second EGF domain mediate binding to platelets and assembly of the factor X activating complex.[6]

The structures of all four domains have been solved. A structure of the two EGF domains and the trypsin-like domain was determined for the pig protein.[7] The structure of the Gla domain, which is responsible for Ca(II)-dependent phospholipid binding, was also determined by NMR.[8]

Several structures of 'super active' mutants have been solved,[9] which reveal the nature of factor IX activation by other proteins in the clotting cascade.

The gene for factor IX is located on the X chromosome (Xq27.1-q27.2) and is therefore X-linked recessive: mutations in this gene affect males much more frequently than females. It was first cloned in 1982 by Kotoku Kurachi and Earl Davie.[10]

Deficiency of factor IX causes Christmas disease (hemophilia B).[1] Over 100 mutations of factor IX have been described; some cause no symptoms, but many lead to a significant bleeding disorder. The original Christmas disease mutation was identified by sequencing of Christmas' DNA, revealing a mutation which changed a cysteine to a serine.[12]Recombinant factor IX is used to treat Christmas disease, and is commercially available as BeneFIX[13] and Alprolix.[14] Some rare mutations of factor IX result in elevated clotting activity, and can result in clotting diseases, such as deep vein thrombosis.[15]

Factor IX deficiency is treated by injection of purified factor IX produced through cloning in various animal or animal cell vectors. Tranexamic acid may be of value in patients undergoing surgery who have inherited factor IX deficiency in order to reduce the perioperative risk of bleeding.[16]

A list of all the mutations in Factor IX is compiled and maintained at the Factor IX mutation database[17] maintained at the University College London.